Browsing by Author "Calderón, FH"

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    PC12 and neuro 2a cells have different susceptibilities to acetylcholinesterase-amyloid complexes, amyloid25-35 fragment, glutamate, and hydrogen peroxide
    (1999) Calderón, FH; Bonnefont, A; Muñoz, FJ; Fernández, V; Videla, LA; Inestrosa, NC
    This work addresses the differential effects of several oxidative insults on two neuronal cell lines, PC12 and Neuro 2a cells, extensively used as neuronal models in vitro, We measured cellular damage using the cytotoxic assays for MTT reduction and LDH release and found that acetylcholinesterase (AChE)-amyloid-beta-peptide (AP) complexes, A beta(25-35) fragment, glutamate and H2O2 were over 200-fold more toxic to PC12 than to Neuro 2a cells, 17 alpha and 17 beta estradiol were able to protect both cell types from damage caused by H2O2 or glutamate, By contrast, other insults not related to oxidative stress, such as those caused by the nonionic detergent Triton X-100 and serum deprivation, induced a similar level of damage in both PC12 and Neuro 2a cells, Considering that the AP peptide, H2O2 and glutamate are cellular insults that cause an increase In reactive oxygen species (ROS), the intracellular levels of the antioxidant compound, glutathione were verified, Neuro 2a cells were found to have 4- to 5-fold more glutathione than PC12 cells, Our results suggest that Neuro 2a cells are less susceptible to exposure to AChE-A beta complexes, A beta(25-35) fragment, glutamate and H2O2 than PC12 cells, due to higher intracellular levels of antioxidant defense factors. (C) 1999 Wiley-Liss, Inc.
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    Stable complexes involving acetylcholinesterase and amyloid-β peptide change the biochemical properties of the enzyme and increase the neurotoxicity of Alzheimer's fibrils
    (1998) Alvarez, A; Alarcón, R; Opazo, C; Campos, EO; Muñoz, FJ; Calderón, FH; Dajas, F; Gentry, MK; Doctor, BP; De Mello, FG; Inestrosa, NC
    Brain acetylcholinesterase (AChE) forms stable complexes with amyloid-beta peptide (A beta) during its assembly into filaments, in agreement with its colocalization with the A beta deposits of Alzheimer's brain. The association of the enzyme with nascent A beta aggregates occurs as early as after 30 min of incubation. Analysis of the catalytic activity of the AChE incorporated into these complexes shows an anomalous behavior reminiscent of the AChE associated with senile plaques, which includes a resistance to low pH, high substrate concentrations, and lower sensitivity to AChE inhibitors. Furthermore, the toxicity of the AChE-amyloid complexes is higher than that of the A beta aggregates alone. Thus, in addition to its possible role as a heterogeneous nucleator during amyloid formation, AChE, by forming such stable complexes, may increase the neurotoxicity of A beta fibrils and thus may determine the selective neuronal loss observed in Alzheimer's brain.